Cervical cancer is one of the leading causes of cancer deaths in women world-wide, killing more than 233,000 women each year. Cervical cancer was the most common malignancy in both incidence and mortality among women prior to the 20th century. The reduction in the incidence of cervical cancer is one of the major public health achievements in developed nations, largely due to the implementation of population-based screening, detection and treatment programs for pre-invasive disease. However, while the incidence of cervical cancer in developed nations has fallen, the disease continues to be the second most common cancer in women worldwide.
Papanicolaou (Pap) smears can detect cervical cancer or pre-cancerous changes in the cervix, many of which are related to HPV. These Pap smears have greatly reduced the incidence and mortality of cervical cancer in developed countries where widespread screening procedures occur. In developing countries where screening procedures are still limited, cervical cancer is the most frequently reported cancer in women, and the incidence continues to rise.
All current treatments for cervical intraepithelial abnormalities, including cryotherapy, laser ablation, excisional conization and loop electrosurgical excision procedure (LEEP), are invasive surgical procedures that often lead to significant side effects including excessive discharge, infection, bleeding, cramping, and cervical incompetence, which may lead to miscarriage, loss of cervical integrity and inability to become pregnant. In addition, these procedures must be performed in an outpatient facility, increasing the cost of treatment.
Cervical intraepithelial neoplasia (CIN) refers to a pre-invasive pathological intermediate to cervical cancer. The abnormalities observed on a cytologic smear or tissue biopsy of the cervix represent alterations in the degree of differentiation of cervical epithelial cells. This cellular dysplasia is categorized into three different groups of severity: CIN I refers to mild dysplasia confined to the basal third of the epithelium; CIN II refers to lesions confined to the basal two-thirds of the epithelium; and CIN III refers to cellular dysplasia encompassing greater than two-thirds of the epithelial thickness.
Approximately 3.5 million women in the United States will have abnormal Pap smear tests each year. Approximately 1.2 million of these women have a squamous intraepithelial lesion (SIL) of which 200,000 to 300,000 are classified as high-grade. The incidence of high-grade CIN in Latin America is more than 3 times that seen in the US. Table 1 provides a summary of the prevalence of HPV infections and CIN worldwide.
TABLE 1Worldwide Prevalence of HPV and CINIncidenceIncidenceHigh-Risk HPVCIN 2/3US1,750,000250,000Europe1,839,200275,880Latin America5,884,110882,616Japan1,173,480176,022
HPV infection is endemic among sexually active individuals. Women who have multiple sexual partners have a higher chance of acquiring HPV and consequently, an HPV-related cervical infection. Infection with high-risk HPV types increases the odds that a woman will develop cervical cancer. Screening for and subsequently treating pre-cancerous cervical conditions is highly effective in the prevention of cervical cancer in HPV-infected women. However, current treatments often require surgical intervention and alternative therapeutic options are needed.